MOLECULAR ELECTROSTATIC POTENTIAL IN DIFFERENTIAL INHIBITION OF PROSTAGLANDIN ENDOPEROXIDE SYNTHASE (CYCLOOXYGENASE) BY NONSTEROIDAL ANTIINFLAMMATORY DRUGS

Molecular electrostatic potentials (MEPs) calculated from MNDO wavefun ctions were compared with ab initio STO-3G, 3-21G and 6-31G* values a nd qualitative agreement was found for diverse classes of nonsteroidal antiinflammatory agents (NSAIDs). The MNDO MEPs present some differen ces with ab initio potentials in describing the electrostatic features of the aromatic molecules examined (meclofenamic, indomethacin, pirpr ofen, and cycloprofen). All compounds showed an extended region with p ositive MEP values and negative potential zones in the neighbourhood o f the carboxyl group. The differences between the central and upper re gions of the MEP distribution obtained for these NSAIDs might explain the time-dependent cyclooxygenase inhibition. (C) 1997 Elsevier Scienc e B.V.